Relaxin does not improve Angiotensin II-induced target-organ damage

PLoS One. 2014 Apr 7;9(4):e93743. doi: 10.1371/journal.pone.0093743. eCollection 2014.

Abstract

Relaxin is a corpus-luteum produced protein hormone with vasodilatatory, anti-fibrotic, and angiogenic properties that are opposite to angiotensin (Ang) II. We investigated whether or not relaxin ameliorates Ang II-induced target-organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGR) that develop severe hypertension, target-organ damage, and die untreated within 7-8 weeks. Recombinant relaxin at a low (26 μg/kg/d) and a high dose (240 μg/kg/d) was given to 4 week-old dTGR and age-matched Sprague-Dawley rats (SD). Systolic blood pressure increased progressively in untreated dTGRs from 162 ± 3 mmHg at week 5 to 225 ± 5 mmHg at week 7. Relaxin had no effect on blood pressure whereas SD rats were normotensive (106 ± 1 mmHg). Untreated and relaxin-treated dTGR had similarly severe cardiac hypertrophy indices. Relaxin did not ameliorate albuminuria and did not prevent matrix-protein deposition in the heart and kidney in dTGR. Finally, relaxin treatment did not reduce mortality. These data suggest that pharmacological doses of relaxin do not reverse severe effects of Ang II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria* / blood
  • Albuminuria* / drug therapy
  • Albuminuria* / genetics
  • Angiotensin II / biosynthesis*
  • Angiotensin II / genetics
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / genetics
  • Cardiomegaly* / blood
  • Cardiomegaly* / drug therapy
  • Cardiomegaly* / genetics
  • Humans
  • Hypertension* / blood
  • Hypertension* / drug therapy
  • Hypertension* / genetics
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Recombinant Proteins / pharmacology
  • Relaxin / pharmacology*
  • Renin / genetics
  • Renin / metabolism

Substances

  • Recombinant Proteins
  • Angiotensin II
  • Relaxin
  • Renin

Grants and funding

The work was funded by grant in aid by Novartis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.